Prognostic value of comorbidities in older patients with cancer: the ELCAPA cohort study.

BACKGROUND: In older patients, comorbidities competed with cancer for mortality risk. We assessed the prognostic value of comorbidities in older patients with cancer. PATIENTS AND METHODS: We analysed all patients >70 years of age with colorectal, breast, prostate, or lung cancer included in the prospective ELCAPA cohort. The Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score was used to assess comorbidities. The primary endpoint was overall survival (OS) at 3, 12, and 36 months. The adjusted difference in the restricted mean survival time (RMST) was used to assess the strength of the relationship between comorbidities and survival. RESULTS: Of the 1551 patients included (median age 82 years; interquartile range 78-86 years), 502 (32%), 575 (38%), 283 (18%), and 191 (12%) had colorectal, breast, prostate, and lung cancer, respectively, and 50% had metastatic disease. Hypertension, kidney failure, and cognitive impairment were the most common comorbidities (67%, 38%, and 29% of the patients, respectively). A CIRS-G score >17, two or more severe comorbidities, more than seven comorbidities, heart failure, and cognitive impairment were independently associated with shorter OS. The greatest effect size was observed for CIRS-G >17 (versus CIRS-G <11): at 36 months, the adjusted differences in the RMST (95% confidence interval) were -6.0 months (-9.3 to -2.6 months) for colorectal cancer, -9.1 months (-13.2 to -4.9 months) for breast cancer, -8.3 months (-12.8 to -3.9 months) for prostate cancer, and -5.5 months (-9.9 to -1.1 months) for lung cancer (P < 0.05 for all). CONCLUSIONS: Comorbidities' type, number, and severity were independently associated with shorter OS. A 17-point cut-off over 56 for the total CIRS-G score could be considered in clinical practice.

Quantitation of pulmonary surfactant protein SP-B in the absence or presence of phospholipids by enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polyclonal or monoclonal anti-surfactant protein SP-B antibodies to quantitate purified SP-B in chloroform/methanol and in chloroform/methanol extracts of whole pulmonary surfactant at nanogram levels. This method has been used to explore the effect of the presence of different phospholipids on the immunoreactivity of SP-B. Both polyclonal and monoclonal antibodies produced reproducible ELISA calibration curves for methanolic SP-B solutions with protein concentrations in the range of 20-1000 ng/mL. At these protein concentrations, neither dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, nor phosphatidylcholine or phosphatidylglycerol from egg yolk had significant effects on the binding of antibodies to SP-B up to protein-to-lipid weight ratios of 1:20. Coating of ELISA plates with SP-B concentrations higher than 1 microg/mL produced a substantial decrease in the binding of antibodies to the protein that was prevented by the presence of negatively charged but not zwitterionic phospholipids. Characterization of the secondary structure of SP-B by far-UV circular dichroism showed that phospholipids induced pronounced changes on the conformation of SP-B when the solvent was evaporated and dry lipid-protein films were formed, a necessary step to expose protein to antibodies in ELISA. Under these conditions, negatively charged lipids, but not zwitterionic ones, induced a marked decrease on the ellipticity of SP-B that would be associated with a conformation that is significantly more exposed to antibodies.

Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers.

Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or 20% (w/w) surfactant protein SP-B have been reconstituted and spread at air-liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from these preparations were qualitatively comparable to the isotherms of the corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out at higher pressures from vesicle-spread films than from solvent-spread monolayers. SP-B caused a marked decrease on the rate of relaxation of DPPC collapse phases to equilibrium pressures in all the lipid/protein films assayed. This stabilizing effect was higher in vesicle-spread than in solvent-spread monolayers. Inclusion in the films of traces of the fluorescent probe NBD-PC (1 mol%) and use of a fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red, allowed for direct observation of protein and lipid domains at the interface by epifluorescence microscopy. Upon compression, SP-B altered the packing of phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction of the area of liquid-condensed domains, in a way similar to its effect in solvent-spread monolayers. SP-B was not associated with condensed regions of the films. Fluorescence images from vesicle-spread films showed discrete fluorescent aggregates that could be consistent with the existence of lipid-protein vesicles in close association with the monolayer. Both the retention of SP-B at higher surface pressures and the greater stability of collapse phases of DPPC/SP-B films prepared by spreading from liposomes in comparison to those spread from solvents can be interpreted as a consequence of formation of complex bilayer-monolayer interacting systems.

[A comparison and synergy in the treatment of essential arterial hypertension]. / Comparación y sinergia en el tratamiento de la hipertensión arterial esencial.

Forty patients with mild or moderate essential hypertension were studied. They received daily doses of either 240 mg verapamil or 10 mg enalapril, as well as a placebo. Total duration of trial was 24 weeks: a "washout" period of 2 weeks, a treatment period of 6 weeks with one of the two drugs, another "washout" period of 2 weeks, and another treatment period of 6 weeks with the alternate drug. Those patients with persistence of diastolic blood pressure (DBP) above 90 mmHg received simultaneously both drugs for an additional period of 8 weeks. Patients were assigned alternately to one of the groups. When each drug was given during the first treatment period, DBP was reduced below 90 mmHg in 15 of 19 patients receiving verapamil, and in 12 of 20 that received enalapril. When the drugs were given during the second treatment period, DBP became normal in 16 of 19 patients receiving enalapril, and in all the 18 patients treated with verapamil. Three patients achieved normal DBP when received simultaneously both drugs. Two patients withdrew from the trial for personal reasons and one for experimenting cough as reaction to enalapril. There were no other undesirable side effects. Laboratory tests did not show changes. Both products were similarly effective. Synergy was shown by the improvement of patients unresponsive to either drug when given singly, but responding when both were given simultaneously.

[Cilazapril, a new ACE inhibitor, in severe arterial hypertension]. / Cilazapril, un nuevo inhibidor de ECA, en la hipertensión arterial severa.

We assessed the efficacy and safety of cilazapril, alone or in combination with hydrochlorothiazide. It was an open trial, that included 14 patients with or more 114 mmHg of diastolic arterial tension. On the first stage of 25 days, the arterial tension was normalized in 5 patients with 10 mg of cilazapril and 7 patients when hydrochlorothiazide was added, 2 patients did not respond. On the second stage of 52 weeks, of the 12 patients whose diastolic arterial tension was normalized, 2 patients remained with normal arterial tension with cilazapril, 5 when hydrochlorothiazide was added and the rest 5 patients did not respond. No undesirable side effects were detected, nor abnormalities in the laboratory tests. The long-term benefit obtained on 50% of patients make evident the usefulness of cilazapril in severe arterial hypertension. Its administration once a day and the absence of side effects increase the interest of its use.